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971.
972.
Diekmann S Weston J Anders E Boland W Schönecker B Hettmann T von Langen J Erhardt S Mauksch M Bräuer M Beckmann C Rost M Sperling P Heinz E 《Journal of biotechnology》2002,90(2):73-94
The Collaborative Research Center (CRC) 436 'Metal-Mediated Reactions Modeled after Nature' was founded for the express purpose of analyzing the catalytic principles of metallo-enzymes in order to construct efficient catalysts on a chemical basis. The structure of the active center and neighboring chemical environment in enzymes serves as a focal point for developing reactivity models for the chemical redesign of catalysts. Instead of simply copying enzyme construction, we strive to achieve new chemical intuition based on the results of long-lasting natural evolution. We hope for success, since nature uses a limited set of building blocks, whereas we can apply the full repertoire of chemistry. Key substrates in this approach are small molecules, such as CO2, O2 NO3- and N2. Nature complexes these substrates, activates them and performs chemical transformations--all within the active center of a metalloenzyme. In this article, we report on some aspects and first results of the Collaborative Research Center (CRC) 436, such as nitrate reductase, sphingolipid desaturase, carbonic anhydrase, leucine aminopeptidase and dopamine beta-monooxygenase. 相似文献
973.
Asfaw B Ledvinová J Dobrovolńy R Bakker HD Desnick RJ van Diggelen OP de Jong JG Kanzaki T Chabas A Maire I Conzelmann E Schindler D 《Journal of lipid research》2002,43(7):1096-1104
Skin fibroblast cultures from patients with inherited lysosomal enzymopathies, alpha-N-acetylgalactosaminidase (alpha-NAGA) and alpha-galactosidase A deficiencies (Schindler and Fabry disease, respectively), and from normal controls were used to study in situ degradation of blood group A and B glycosphingolipids. Glycosphingolipids A-6-2 (GalNAc (alpha 1-->3)[Fuc alpha 1-->2]Gal(beta1-->4)GlcNAc(beta 1-->3)Gal(beta 1--> 4)Glc (beta 1-->1')Cer, IV(2)-alpha-fucosyl-IV(3)-alpha-N-acetylgalactosaminylneolactotetraosylceramide), B-6-2 (Gal(alpha 1-->3)[Fuc alpha 1--> 2] Gal (beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc(beta 1-->1')Cer, IV(2)- alpha-fucosyl-IV(3)-alpha-galactosylneolactotetraosylceramide), and globoside (GalNAc(beta 1-->3)Gal(alpha 1-->4)Gal(beta 1-->4)Glc(beta 1-->1') Cer, globotetraosylceramide) were tritium labeled in their ceramide moiety and used as natural substrates. The degradation rate of glycolipid A-6-2 was very low in fibroblasts of all the alpha-NAGA-deficient patients (less than 7% of controls), despite very heterogeneous clinical pictures, ruling out different residual enzyme activities as an explanation for the clinical heterogeneity. Strongly elevated urinary excretion of blood group A glycolipids was detected in one patient with blood group A, secretor status (five times higher than upper limit of controls), in support of the notion that blood group A-active glycolipids may contribute as storage compounds in blood group A patients. When glycolipid B-6-2 was fed to alpha-galactosidase A-deficient cells, the degradation rate was surprisingly high (50% of controls), while that of globotriaosylceramide was reduced to less than 15% of control average, presumably reflecting differences in the lysosomal enzymology of polar glycolipids versus less-polar ones. Relatively high-degree degradation of substrates with alpha-D-Galactosyl moieties hints at a possible contribution of other enzymes. 相似文献
974.
Although the content of intramuscular fat (IMF) influences significantly meat quality, it can be estimated only after the slaughter of animals. Variants of the H-FABP gene were suggested as candidate genes influencing the variability of IMF. The effect of H-FABP - HinfI polymorphism on the content of IMF, backfat thickness, the weight and percentages of major meat parts and of the leg in carcass weight was studied in a group of 97 pigs (46 gilts and 51 barrows) of Large White and Landrace breeds using the test of fattening capacity and carcass value. In the set of experimental animals, the frequencies of genes were H = 0.75 +/- 0.03 and h = 0.25 +/- 0.03. Biometric analyses did not corroborate differences among different H-FABP - HinfI genotypes and all the traits under study. Only in genotypes HH and Hh the differences between least-square means of phenotypic IMF values under study were close to the limit of significance (P = 0.06). 相似文献
975.
Tumor growth and invasion are not only the result of malignant transformation but are also dependent on environmental influences from surrounding stroma, extracellular matrix (ECM), local cytokines and systemic hormones. We have investigated the influence of ECM components on three human breast cancer cell lines of different malignant potential: MCF-7, T47D and MDA-MB-231 were cultured on collagen I, collagen IV, laminin, fibronectin or poly-D-lysine, and we analyzed the proliferation rate and cytokine expression pattern. Among the three cell lines investigated we observed a distinct response to each ECM component. We hypothesize that ECM may have a significant modulatory effect on malignant behavior in vivo which might depend on individual responses and on the differentiation state of tumor cells. This study also shows that the surface on which cells are cultured greatly influences cell kinetics and the cytokine expression pattern. 相似文献
976.
The erythropoietin receptor transduces signals leading to the growth, differentiation, and survival of red blood cell precursors via interaction with Janus kinase 2 (JAK2). This interaction was thought to occur only at the plasma membrane. Recent evidence, however, shows that JAK2 assembles with newly synthesized erythropoietin receptors in the endoplasmic reticulum, and that this assembly is essential for efficient expression of the receptors at the cell surface. 相似文献
977.
Separation of carbamazepine and five metabolites,and analysis in human plasma by micellar electrokinetic capillary chromatography 总被引:1,自引:0,他引:1
Raggi MA Pucci V Maurizio A Muzikar J Kenndler E 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,770(1-2):217-225
A rapid and feasible method was developed for the analysis of carbamazepine and its five metabolites (10,11-dihydro-10,11-epoxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine, 10,11-dihydro-10-hydroxycarbamazepine, 2-hydroxycarbamazepine and 3-hydroxycarbamazepine) in human plasma. Separation of the analytes is based on micellar electrokinetic chromatography, in untreated fused-silica capillary (48.5/40.0 cm length, 50 microm I.D.) with phosphate buffer (30 mM, pH 8.00) as background electrolyte, containing 50 mM sodium dodecylsulfate, and methanol (15%, v/v) as organic modifier. Clean up of human plasma samples was carried out by means of a solid-phase extraction procedure, which gave a high extraction yield for all six carbamazepines (>88%). The overall precision of the method gives a mean RSD of about 1.8%. The limit of quantitation for all analytes is < or = 0.30 microg ml(-1), the limit of detection < or = 0.12 microg ml(-1). 相似文献
978.
D. Zink T. Cremer Rainer Saffrich Roger Fischer Michael F. Trendelenburg Wilhelm Ansorge Ernst H. K. Stelzer 《Human genetics》1998,102(2):241-251
A new approach is presented which allows the in vivo visualization of individual chromosome territories in the nuclei of
living human cells. The fluorescent thymidine analog Cy3-AP3-dUTP was microinjected into the nuclei of cultured human cells,
such as human diploid fibroblasts, HeLa cells and neuroblastoma cells. The fluorescent analog was incorporated during S-phase
into the replicating genomic DNA. Labelled cells were further cultivated for several cell cycles in normal medium. This well-known
scheme yielded sister chromatid labelling. Random segregation of labelled and unlabelled chromatids into daughter nuclei resulted
in nuclei exhibiting individual in vivo detectable chromatid territories. The territories were composed of subcompartments
with diameters ranging between approximately 400 and 800 nm which we refer to as subchromosomal foci. Time-resolved in vivo
studies demonstrated changes of positioning and shape of territories and subchromosomal foci. The hypothesis that subchromosomal
foci persist as functionally distinct entities was supported by double labelling of chromatin with CldU and IdU, respectively,
at early and late S-phase and subsequent cultivation of corresponding cells for 5–10 cell cycles before fixation and immunocytochemical
detection. This scheme yielded segregated chromatid territories with distinctly separated subchromosomal foci composed of
either early- or late-replicating chromatin. The size range of subchromosomal foci was similar after shorter (2 h) and longer
(16 h) labelling periods and was observed in nuclei of both living and fixed cells, suggesting their structural identity.
A possible functional relevance of chromosome territory compartmentalization into subchromosomal foci is discussed in the
context of present models of interphase chromosome and nuclear architecture.
Received: 10 November 1997 / Accepted: 24 November 1997 相似文献
979.
Ernst J. Kuipers Dawn A. Israel Johannes G. Kusters Martin J. Blaser 《Journal of bacteriology》1998,180(11):2901-2905
Many strains of Helicobacter pylori are naturally competent for transformation in vitro. Since there is a high degree of genetic variation among H. pylori strains, we sought to determine whether mechanisms of DNA exchange other than transformation exist in these organisms. Studies were done with H. pylori cells that each were resistant to two different antibiotics; the procedure used involved mating of cells on plates or in broth, in the absence or presence of DNase. In each experiment, such matings produced progeny with the markers of both parents. Examination of the full resistance profile and random arbitrarily primed DNA PCR (RAPD-PCR) profiles of the progeny indicated that DNA transfer was bidirectional. DNase treatment reduced but did not eliminate transfer; only the presence of both DNase and a membrane separating the cells did so. For progeny derived from matings in the presence of DNase, antibiotic resistance and RAPD profiles indicated that transfer was unidirectional. DNase-treated cell-free supernatants also did not transform, ruling out transduction. These experiments indicate that both a DNase-sensitive mechanism (transformation) and a DNase-resistant conjugation-like mechanism involving cell-to-cell contact may contribute to DNA transfer between H. pylori cells. 相似文献
980.
Distribution of cadmium in leaves of cadmium tolerant and sensitive ecotypes of Silene vulgaris 总被引:3,自引:0,他引:3
Agnes N. Chardonnens Wilma M. ten Bookum Lothar D. J. Kuijper Jos A. C. Verkleij Wilfried H. O. Ernst 《Physiologia plantarum》1998,104(1):75-80
It has been postulated that vacuolar compartmentation might play an important role in naturally selected cadmium tolerance in Silene vulgaris (Moench.) Garcke (Bladder campion). Additionally, a tendency of heavy metals to accumulate in the epidermis has been reported. Since these factors would affect the distribution of cadmium in leaves, we determined the distribution of cadmium in leaves of cadmium tolerant and sensitive ecotypes of Silene vulgaris at different levels of exposure and at different time intervals. Cadmium concentrations were higher in leaves of sensitive plants than in those of cadmium tolerant ones after identical exposure to cadmium for a period of 8 days. The highest cadmium concentrations were found in the lower epidermis of plants of both ecotypes. The amount of cadmium located at the lower epidermis was highest for sensitive plants, although the stomatal density was lower in the sensitive ecotype than in the tolerant one. A possible explanation for this phenomenon is the weak relationship between transpiration (water flow) and element allocation. Our results support the hypothesis that vacuolar storage of cadmium plays an important role in the mechanism of cadmium tolerance in Silene vulgaris . 相似文献